Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in
allogeneic cellular medicines for inflammatory diseases, today
announced publication of the DREAM-HF Phase 3 trial results in the
premier peer-reviewed journal for cardiovascular medicine, the
Journal of the American College of Cardiology (JACC). The results
of the randomized, double-blind, controlled study in 537 patients
showed that Mesoblast’s mesenchymal precursor cell therapy (MPCs;
rexlemestrocel-L) strengthened heart function at 12 months, as
measured by left ventricular ejection fraction (LVEF) and decreased
cardiovascular death, myocardial infarction (MI) or stroke in
patients with chronic heart failure (CHF) due to reduced ejection
fraction (HFrEF) over a mean follow-up of 30 months.1
DREAM-HF’s lead investigator, Dr. Emerson C.
Perin, MD, PhD, FACC, Medical Director at The Texas Heart
Institute, said, “The cells appear to work by reducing
inflammation, increasing microvascular flow, and strengthening
heart muscle. Locally, in the heart, the MPCs can protect cardiac
muscle cells from dying and can improve blood flow and energetics.
In large blood vessels throughout the body, the reduced
inflammation resulting from the activation of MPCs may decrease
plaque instability, which is what leads to heart attacks and
strokes. The cells seem to have a systemic immune modulatory and
anti-inflammatory effect.”
“MPC therapy could change the future of
cardiovascular care for patients with heart failure due to
inflammation,” according to Dr. Joseph G. Rogers, CEO and President
of The Texas Heart Institute and advanced heart failure
specialist.
The study enrolled patients across 51 sites in
North America and the results showed that a single intra-myocardial
injection of 150 million cells of rexlemestrocel-L:
- improved LVEF from baseline to 12
months to a significantly greater extent than controls across all
patients with available echocardiograms (p=0.021), with maximal
benefit seen in patients with active inflammation as measured by
the presence of baseline hsCRP ≥2mg/L (p=0.008)
- reduced risk of MI or stroke by 57%
(HR 0.43; 95% CI [0.23, 0.78]) in all treated patients compared
with controls
- reduced risk of MI or stroke by 75%
(HR 0.25; 95% CI [0.09, 0.68]) in patients with inflammation
(baseline hsCRP ≥2mg/L) compared with controls
- reduced risk for time-to-first
Major Adverse Cardiac Event (MACE), defined as cardiovascular
death, MI or stroke, by 28% (HR 0.72; 95% CI: [0.51, 1.03]) in
all-treated patients compared with controls
- reduced risk for time-to-first MACE
by 37% (HF 0.63; 95% CI: [0.39, 1.02]) in patients with
inflammation (baseline hsCRP≥2mg/L) compared with controls
- did not further reduce the
frequency of recurrent hospitalizations for worsening HF symptoms
when added to maximal standard of care medicines for heart
failure.
“These provocative results may usher in new
directions for the field of cell-based regenerative therapies in
the coming decade,” stated PV Johnston et al commenting on the
DREAM-HF results in a recently published2 review in American Heart
Journal Plus: Cardiology Research. “Using the knowledge gained from
DREAM-HF along with the trials that preceded it, the potential for
breakthrough cell-based therapies for heart failure in the coming
decade is immense.”
“We are very encouraged by these study data that
indicate the potential of our allogeneic cellular therapy to
address the major areas of unmet need in heart failure patients
where conventional treatments are not effective,” said Mesoblast
CEO Dr. Silviu Itescu. “Improvement in LVEF at 12 months may be a
functional surrogate endpoint for rexlemestrocel-L’s subsequent
benefits on long-term MACE outcomes and survival in this high-risk
patient population with chronic heart failure.”
“These findings suggest an important mechanism
of action is the anti-inflammatory effect of MPCs, but perhaps more
importantly, these effects are systemic and not limited to their
site of delivery in the heart,” added PV Johnston et al. “The
results of DREAM-HF suggest those patients with heart failure with
preserved ejection fraction (HFpEF) and other cardiomyopathies
could potentially benefit from MPC therapy as well. The results of
DREAM-HF in this way mirror the prior Cardiothoracic Surgical
Trials Network studies of intramyocardial MPCs in left ventricular
assist device (LVAD) patients.”
In an earlier randomized, controlled trial in
159 patients with end-stage chronic HFrEF, inflammation and LVAD
implantation, a single intervention with rexlemestrocel-L injected
directly into the left ventricle at the time of LVAD insertion
resulted in significantly reduced cumulative incidence of
life-threatening non-surgical major mucosal bleeding events
requiring hospitalization through 6 months (GI or epistaxis)
compared with controls (p=0.02).
Mesoblast plans to meet with the US Food &
Drug Administration (FDA) next quarter under its existing
regenerative medicine advanced therapy (RMAT) designation to
discuss common mechanisms- of-action across the spectrum of chronic
HFrEF patients from NYHA class II/III to those with an implanted
LVAD, and potential pathway to marketing approval.
About Chronic Heart Failure
Chronic heart failure (CHF) is characterized by poor heart function
resulting in insufficient blood flow to the body’s vital organs and
extremities. This condition affects approximately 6.5 million
people in the United States and 26 million people globally with
increasing prevalence and incidence. CHF patients are commonly
classified according to the New York Heart Association (NYHA)
categories based on the patient’s physical limitations. Class I
(mild) patients have no limitations while Class IV patients
(severe/end stage) experience symptoms even at rest.
The mortality rate approaches 50% at 5 years as
patients progress beyond NYHA early class II disease in parallel
with increasing inflammation in the heart and in the
circulation.3,4 Despite recent approvals of new therapies for
HFrEF, NYHA class II/III HFrEF patients with inflammation remain at
high risk for cardiac death, heart attacks and strokes.
Over 60,000 patients annually in the US progress
to end-stage heart failure (NYHA class IIIB/IV) and these patients
have a one-year mortality exceeding 50%.5 Use of LVADs in end-stage
heart failure patients to improve survival is gaining momentum,
with approximately 5,500 LVADs implanted annually in the US.6-8
However, systemic inflammation associated with major
life-threatening gastrointestinal bleeding high rates of
rehospitalization remain a major obstacle to greater LVADs
use.9,10
About Mesoblast Mesoblast is a
world leader in developing allogeneic (off-the-shelf) cellular
medicines for the treatment of severe and life-threatening
inflammatory conditions. The Company has leveraged its proprietary
mesenchymal lineage cell therapy technology platform to establish a
broad portfolio of late-stage product candidates which respond to
severe inflammation by releasing anti-inflammatory factors that
counter and modulate multiple effector arms of the immune system,
resulting in significant reduction of the damaging inflammatory
process.
Mesoblast has a strong and extensive global
intellectual property portfolio with protection extending through
to at least 2041 in all major markets. The Company’s proprietary
manufacturing processes yield industrial-scale, cryopreserved,
off-the-shelf, cellular medicines. These cell therapies, with
defined pharmaceutical release criteria, are planned to be readily
available to patients worldwide.
Mesoblast is developing product candidates for
distinct indications based on its remestemcel-L and
rexlemestrocel-L allogeneic stromal cell technology platforms.
Remestemcel-L is being developed for inflammatory diseases in
children and adults including steroid refractory acute graft versus
host disease, biologic-resistant inflammatory bowel disease, and
acute respiratory distress syndrome. Rexlemestrocel-L is in
development for advanced chronic heart failure and chronic low back
pain. Two products have been commercialized in Japan and Europe by
Mesoblast’s licensees, and the Company has established commercial
partnerships in Europe and China for certain Phase 3 assets.
Mesoblast has locations in Australia, the United
States and Singapore and is listed on the Australian Securities
Exchange (MSB) and on the Nasdaq (MESO). For more information,
please see www.mesoblast.com, LinkedIn: Mesoblast Limited and
Twitter: @Mesoblast
References / Footnotes
- Perin EC. Et al. Randomized Trial
of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in
Patients With Heart Failure. JACC Vol. 81, No. 9, 2023.
https://doi.org/10.1016/j.jacc.2022.11.061
- Johnston PV. et al. Dare to Dream?
Cell-based therapies for heart failure after DREAM-HF: Review and
roadmap for future clinical study. American Heart Journal Plus:
Cardiology Research and Practice 13 (2022) 100118.
https://doi.org/10.1016/j.ahjo.2022.100118
- AHA’s 2017 Heart Disease and Stroke
Statistics
- Ponikowski P., et al. Heart
Failure: Preventing disease and death worldwide. European Society
of Cardiology. 2014; 1: 4-25
- Gustafsson F, Rogers JG. Left
ventricular assist device therapy in advanced heart failure:
patient selection and outcomes. European Journal of Heart Failure
2017;19:595-602.
- United Network for Organ
Sharing
- Agency for Healthcare Research and
Quality – Healthcare Cost and Utilization Project – Claims Analysis
ICD- 37.6.
- Data on file
- Chatterjee A, Feldmann C, Hanke JS
(2018) The momentum of HeartMate 3: a novel active magnetically
levitated centrifugal left ventricular assist device (LVAD). J
Thorac Dis 10 (Suppl 15): S1790-S1793.
- Mehra, MR Salerno C, Cleveland JC
(2018) Health care resources use and cost implications in the
MOMENTUM 3 long-term outcome study: a randomized controlled trial
of a magnetically levitated cardiac pump in advanced heart
failure.
Forward-Looking StatementsThis
press release includes forward-looking statements that relate to
future events or our future financial performance and involve known
and unknown risks, uncertainties and other factors that may cause
our actual results, levels of activity, performance or achievements
to differ materially from any future results, levels of activity,
performance or achievements expressed or implied by these
forward-looking statements. We make such forward-looking statements
pursuant to the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995 and other federal securities laws.
Forward-looking statements should not be read as a guarantee of
future performance or results, and actual results may differ from
the results anticipated in these forward-looking statements, and
the differences may be material and adverse. Forward-looking
statements include, but are not limited to, statements about: the
initiation, timing, progress and results of Mesoblast’s preclinical
and clinical studies, and Mesoblast’s research and development
programs; Mesoblast’s ability to advance product candidates into,
enroll and successfully complete, clinical studies, including
multi-national clinical trials; Mesoblast’s ability to advance its
manufacturing capabilities; the timing or likelihood of regulatory
filings and approvals, manufacturing activities and product
marketing activities, if any; the commercialization of Mesoblast’s
product candidates, if approved; regulatory or public perceptions
and market acceptance surrounding the use of stem-cell based
therapies; the potential for Mesoblast’s product candidates, if any
are approved, to be withdrawn from the market due to patient
adverse events or deaths; the potential benefits of strategic
collaboration agreements and Mesoblast’s ability to enter into and
maintain established strategic collaborations; Mesoblast’s ability
to establish and maintain intellectual property on its product
candidates and Mesoblast’s ability to successfully defend these in
cases of alleged infringement; the scope of protection Mesoblast is
able to establish and maintain for intellectual property rights
covering its product candidates and technology; estimates of
Mesoblast’s expenses, future revenues, capital requirements and its
needs for additional financing; Mesoblast’s financial performance;
developments relating to Mesoblast’s competitors and industry; and
the pricing and reimbursement of Mesoblast’s product candidates, if
approved. You should read this press release together with our risk
factors, in our most recently filed reports with the SEC or on our
website. Uncertainties and risks that may cause Mesoblast’s actual
results, performance or achievements to be materially different
from those which may be expressed or implied by such statements,
and accordingly, you should not place undue reliance on these
forward-looking statements. We do not undertake any obligations to
publicly update or revise any forward-looking statements, whether
as a result of new information, future developments or
otherwise.
Release authorized by the Chief Executive.
For more information, please contact:
Corporate Communications / Investors |
Media |
Paul Hughes |
BlueDot Media |
T: +61 3 9639 6036 |
Steve Dabkowski |
E: investors@mesoblast.com |
T: +61 419 880 486 |
|
E: steve@bluedot.net.au |
|
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|
Rubenstein |
|
Tali Mackay |
|
E: tmackay@rubenstein.com |
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